The overall goal of the proposed epidemiologic study is to examine the causes and consequences of impaired decision-making in old age. Decision-making refers to the ability to generate and process multiple competing alternatives and choose a favorable behavior. Virtually all behaviors result from some decision-making process, and efficient decision-making is thought to be critical for maintaining independence, health and well-being in modern society. Emerging data suggest that older persons, even some without dementia, exhibit impaired decision-making, and impaired decision-making may be a sign of preclinical Alzheimer's disease (AD). However, surprisingly few studies have rigorously examined decision-making in older persons and longitudinal data are sorely lacking. The proposed study will quantify the rate of change in financial, healthcare, and socioemotional decision-making in a large cohort of community-based older persons without dementia and test the hypothesis that impaired decision-making is associated with adverse health outcomes (i.e., decreased well-being, disability, nursinghome placement, dementia, and death). Further, we will examine the role of affective and contextual factors in decision-making and test the hypothesis that select affective and contextual factors can sustain decision-making even in the face of cognitive decline. Finally, in an effort to understand the neurobiologic basis of impaired decision-making, we will test the hypothesis that AD pathology contributes to impaired decision-making in older persons without dementia who come to autopsy. The proposed study will capitalize on the unique infrastructure provided by the Rush Memory and Aging Project (R01AG17917), a large ongoing epidemiologic clinical-pathologic study of aging and AD, and will quantify decision-making and new pathologic indices in more than 800 community-based participants without dementia;all have agreed to detailed annual clinical evaluations including cognitive assessments and brain donation. By linking the newly collected data on decision-making and AD pathology in brain regions that subserve decision-making with the available data from the Memory and Aging Project, we will have an unprecedented opportunity to examine the causes and consequences of impaired decision-making in old age. Knowledge of the causes and consequences of impaired decision-making is essential for the development of effective interventions to promote independence, health, and well-being in old age. PUBLIC HEALTH RELEVANCE: The proposed study has the potential to generate new knowledge with important public health implications. Older persons are faced with a host of decisions that are critical for maintaining independence, health and well-being in modern society, and finding that a sizeable number of older persons without dementia exhibit impaired decision-making would suggest an immediate need for interventions and public policy efforts to promote efficient decision-making in aging. Further, knowledge of the causes and consequences of impaired decision-making is essential for the development of such interventions and, to the extent that AD pathology underlies impaired decision-making, may suggest that a much larger group of persons including those without overt dementia ultimately may benefit from effective treatment and prevention strategies developed for AD.